Mol._Cell._Biol.-2009-Outwin-4363-75.pdf (1.98 MB)
Smc5-Smc6-dependent removal of cohesin from mitotic chromosomes
journal contribution
posted on 2023-06-08, 13:32 authored by Emily OutwinEmily Outwin, Anja Irmisch, Jo Murray, Matthew J O'ConnellThe function of the essential cohesin-related Smc5-Smc6 complex has remained elusive, though hypomorphic mutants have defects late in recombination, in checkpoint maintenance, and in chromosome segregation. Recombination and checkpoints are not essential for viability, and Smc5-Smc6-null mutants die in lethal mitoses. This suggests that the chromosome segregation defects may be the source of lethality in irradiated Smc5-Smc6 hypomorphs. We show that in smc6 mutants, following DNA damage in interphase, chromosome arm segregation fails due to an aberrant persistence of cohesin, which is normally removed by the Separase-independent pathway. This postanaphase persistence of cohesin is not dependent on DNA damage, since the synthetic lethality of smc6 hypomorphs with a topoisomerase II mutant, defective in mitotic chromosome structure, is also due to the retention of cohesin on undamaged chromosome arms. In both cases, Separase overexpression bypasses the defect and restores cell viability, showing that defective cohesin removal is a major determinant of the mitotic lethality of Smc5-Smc6 mutants
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Publication status
- Published
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- Published version
Journal
Molecular and Cellular BiologyISSN
0270-7306Publisher
American Society for MicrobiologyExternal DOI
Issue
16Volume
29Page range
4363-4375Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2012-11-13First Open Access (FOA) Date
2016-03-22First Compliant Deposit (FCD) Date
2016-11-10Usage metrics
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